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Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse.

Research paper by Riva R Verma, Jun Zhi JZ Er, Ren Wei RW Pu, Jameelah J Sheik Mohamed, Ross A RA Soo, Harish Mithiran HM Muthiah, John Kit Chung JKC Tam, Jeak Ling JL Ding

Indexed on: 07 Jul '20Published on: 07 Jul '20Published in: Frontiers in immunology



Abstract

Recent studies have attempted to uncover the role of Group 1 Innate lymphoid cells (ILCs) in multiple physiological contexts, including cancer. However, the definition and precise contribution of Group 1 ILCs (constituting ILC1 and NK subsets) to metastasis is unclear due to the lack of well-defined cell markers. Here, we first identified ILC1 and NK cells in NSCLC patient blood and differentiated them based on the expression of transcription factors, T-bet and Eomes. Interestingly, Eomes downregulation in the peripheral blood NK cells of NSCLC patients positively correlated with disease progression. Additionally, we noted higher Eomes expression in NK cells (T-betEomes) compared to ILC1s (T-betEomes). We asked whether the decrease in Eomes was associated with the conversion of NK cells into ILC1 using Eomes as a reliable marker to differentiate ILC1s from NK cells. Utilizing a murine model of experimental metastasis, we observed an association between increase in metastasis and Eomes downregulation in NKp46NK1.1 Group 1 ILCs, which was consistent to that of human NSCLC samples. Further confirmation of this trend was achieved by flow cytometry, which identified tissue-specific Eomes ILC1-like and Eomes NK-like subsets in the murine metastatic lung based on cell surface markers and adoptive transfer experiments. Next, functional characterization of these cell subsets showed reduced cytotoxicity and IFNγ production in Eomes ILC1s compared to Eomes cells, suggesting that lower Eomes levels are associated with poor cancer immunosurveillance by Group 1 ILCs. These findings provide novel insights into the regulation of Group 1 ILC subsets during metastasis, through the use of Eomes as a reliable marker to differentiate between NK and ILC1s. Copyright © 2020 Verma, Er, Pu, Sheik Mohamed, Soo, Muthiah, Tam and Ding.

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